Louise Lacalendola Tundisi1,2, Rong Yang1, Luiz Phellipe Pozzuto Borelli3, Thais Alves4, Manisha Mehta1, Marco Vinícius Chaud4, Priscila Gava Mazzola3, Daniel S Kohane5. 1. Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Harvard Institutes of Medicine - 4 Blackfan Circle, Room 914, Boston, MA, zip code 02115, USA. 2. Graduate Program in Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. 3. Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. 4. LaBNUS - Biomaterials and Nanotechnology Laboratory, University of Sorocaba, Sorocaba, SP, Brazil. 5. Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Harvard Institutes of Medicine - 4 Blackfan Circle, Room 914, Boston, MA, zip code 02115, USA. Daniel.Kohane@childrens.harvard.edu.
Abstract
PURPOSE: Topical therapy of local disease (e.g. skin) is advantageous over oral therapy since there is less systemic drug distribution (so fewer side-effects), no first-pass effect, etc. However, patient compliance with topical therapy can be poor as it may require many applications a day and can last months. Here we propose a topical controlled release formulation with thermoresponsive gelation at body temperature and improved adhesiveness, making it easier to remain in contact with the body. METHODS: The formulation contains two excipients, poloxamer 407 (P407) and casein. Casein can modify the properties of the hydrogel through molecular entanglement. In addition, tissue reaction and drug release profile were evaluated. RESULTS: Changes in casein concentration affected adhesive strength, viscosity, mechanical properties and drug release, presumably by hydrophobic interactions between casein and P407. Two different concentrations of P407 were tested with two different concentrations of casein. Formulations containing 5% and 10% casein released 80% of model drug in 48 h, while formulations without casein released the same fraction in around 24 h hours. Formulations with 10% casein had almost twice the adhesive strength of those without casein. CONCLUSIONS: Addition of casein modified the mechanical properties and drug release rate of the hydrogel. There was no inflammation or injury after brief exposure in vivo.
PURPOSE: Topical therapy of local disease (e.g. skin) is advantageous over oral therapy since there is less systemic drug distribution (so fewer side-effects), no first-pass effect, etc. However, patient compliance with topical therapy can be poor as it may require many applications a day and can last months. Here we propose a topical controlled release formulation with thermoresponsive gelation at body temperature and improved adhesiveness, making it easier to remain in contact with the body. METHODS: The formulation contains two excipients, poloxamer 407 (P407) and casein. Casein can modify the properties of the hydrogel through molecular entanglement. In addition, tissue reaction and drug release profile were evaluated. RESULTS: Changes in casein concentration affected adhesive strength, viscosity, mechanical properties and drug release, presumably by hydrophobic interactions between casein and P407. Two different concentrations of P407 were tested with two different concentrations of casein. Formulations containing 5% and 10% casein released 80% of model drug in 48 h, while formulations without casein released the same fraction in around 24 h hours. Formulations with 10% casein had almost twice the adhesive strength of those without casein. CONCLUSIONS: Addition of casein modified the mechanical properties and drug release rate of the hydrogel. There was no inflammation or injury after brief exposure in vivo.
Entities:
Keywords:
casein; drug delivery; mixed micelles; poloxamer 407; topical treatment
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